An important developmental change commonly associated with aging is skeletal muscle atrophy. Senile muscle atrophy results in decreased mass and associated muscle weakness. These changes, in turn, restrict mobility and independence which have dramatic physical, emotional, and social ramifications in our society. The proposed research is designed to study cellular and molecular change in skeletal muscle during the aging process. In view of the role of skeletal muscle satellite cells in regulating muscle hypertrophy and regeneration, it is conceivable that satellite cell dysfunction in aging muscle could contribute to senile muscle atrophy. The progressive incompetence of this population of myogenic stem cells could result in failure to respond to normal physiological signals which are intended to elicit cell proliferation, fusion into muscle fibers, and muscle protein synthesis. Alterations in the following two fundamental biological processes carried out by satellite cells will be studied as a function of age: (1) proliferation of cultured satellite cells and (2) muscle protein accumulation by satellite cell-derived muscle fibers in culture. Furthermore, the research will evaluate the ability of aging satellite cells to respond to anabolic hormones. Changes in the ability of testosterone or growth hormone to stimulate proliferation will be studied in cultures of satellite cells derived from rats ranging in age from 1-3 days through 24-30 months. In addition, age-related changes in the effect of growth hormone and testosterone on the accumulation of a muscle specific protein, alpha-actin, in cultured satellite cells will also be investigated. This research is designed to provide new insights into fundamental cellular and molecular aspects of muscle aging with the ultimate goal of contributing toward the alleviation of problems associated with senile muscle atrophy.